T Cell Tolerance to Tumors and Cancer Immunotherapy

  • Kimberly Shafer-Weaver
  • Michael Anderson
  • Anatoli Malyguine
  • Arthur A. Hurwitz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


It is widely recognized that the immune system plays a role in cancer progression and that some tumors are inherently immunogenic. The identification of tumor-associated antigens (TAAs) has stimulated research focused on immunotherapies to mediate the regression of established tumors. Cancer-specific immunity has traditionally been aimed at activating CD8+ cytotoxic T lymphocytes (CTLs) directed against major histocompatibility complex (MHC) class I-binding peptide epitopes. Other approaches utilize T cell adoptive therapy where autologous, tumor-specific T cells propagated in vitro are transferred back into recipients. However, these strategies have met with limited success in part due to the regulatory mechanisms of T cell tolerance, which poses a considerable challenge to cancer immunotherapy. Our laboratory utilizes the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, a murine model of prostate cancer, to study mechanisms of T cell tolerization to tumor antigens. We previously demonstrated that upon encounter with their cognate antigen in the tumor microenvironment, naïve T cell become tolerized. Our ongoing studies are testing whether provision of CD4+ T cells can enhance tumor immunity by preventing CD8+ T cell tolerance. A greater understanding of the interaction between various tumor-specific T cell subsets will facilitate the design of novel approaches to stimulate a more potent antitumor immune response.


Major Histocompatibility Complex Tumor Antigen Cancer Immunotherapy Antitumor Immune Response Tumor Immunity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Kimberly Shafer-Weaver
    • 1
  • Michael Anderson
    • 2
  • Anatoli Malyguine
    • 1
  • Arthur A. Hurwitz
    • 2
  1. 1.Applied and Developmental Research Support ProgramSAIC-Frederick Inc., NCI-FrederickFrederickUSA
  2. 2.Tumor Immunity and Tolerance Section, Laboratory of Molecular ImmunoregulationCancer and Inflammation Program, CCR, NIHFrederickUSA

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